Spanish multidisciplinary Consensus on the diagnosis and management of laryngopharyngeal reflux (ReFaL Consensus)

Abstract

Introduction

Laryngopharyngeal reflux (LPR) represents a diagnostic and therapeutic challenge due to the nonspecific nature of its clinical manifestations and the absence of objective biomarkers. The aim of this work is to establish a national consensus on its definition, diagnosis, and treatment through a modified Delphi methodology that integrates the perspectives of otolaryngologists (ENT) and gastroenterologists (GI).

Materials and methods

A scientific committee composed of three ENTs and two GIs developed 117 items distributed across seven thematic sections. The Delphi process involved 73 panellists in the first round, of whom 65 (89%) completed both rounds of voting. Participants were representative of the Spanish autonomous communities, with an average of 17 years of clinical experience and a multidisciplinary profile (63.1% ENT; 36.9% GI).

Results

After two rounds of voting, positive consensus was reached on 76 items (64.9%), distributed as follows: 14 on definition and pathophysiology; 12 on symptoms and pharyngeal findings; 2 on associations with other ENT diseases; 10 on diagnostic methods; 3 on validated questionnaires; 15 on treatment and recommendations; and 11 on clinical follow-up.

Conclusion

The results of the consensus reflect the suitability and effectiveness of the Delphi methodology used to create a consensus document on the definition, presentation, diagnosis, and management of a condition that until now has been poorly defined, such as LPR. The aim is to support specialists in their daily clinical practice, and unlike previous efforts, it has succeeded in unifying within a single document the criteria of the two specialties most involved in managing these patients.

Resumen

Introducción

El reflujo faringolaríngeo (RFL) representa un desafío diagnóstico y terapéutico debido a la inespecificidad de sus manifestaciones clínicas y la ausencia de biomarcadores objetivos. Este trabajo tiene como objetivo establecer un consenso nacional sobre su definición, diagnóstico y tratamiento, mediante una metodología Delphi modificada que integre la visión de otorrinolaringólogos (ORL) y especialistas en aparato digestivo (AD).

Materiales y métodos

Se conformó un comité científico compuesto por tres ORL y dos AD que elaboró 117 ítems distribuidos en siete bloques temáticos. El proceso Delphi contó con la participación de 73 panelistas en la primera ronda, de los cuales 65 (89%) completaron ambas rondas de votación. Los participantes eran representativosde las comunidades autónomas españolas, con una media de 17 años de experiencia clínica, y un perfil multidisciplinar (63,1% ORL; 36,9% AD).

Resultados

Tras dos rondas de votación, se alcanzó consenso positivo en 76 ítems (64,9%), distribuidos de la siguiente manera: 14 sobre definición y fisiopatología; 12 sobre síntomas y hallazgos faríngeos; 2 sobre asociaciones con otras enfermedades ORL; 10 sobre métodos diagnósticos; 3 sobre cuestionarios validados; 15 sobre tratamiento y recomendaciones; y 11 sobre seguimiento clínico.

Conclusión

Los resultados del consenso reflejan la idoneidad y la eficacia de la metodología Delphi empleada para crear un documento de consenso sobre la definición, presentación, diagnóstico y manejo de una patología poco definida hasta ahora como el RFL, cuyo objetivo es ayudar a los especialistas en su práctica clínica diaria y que, a diferencia de otros, ha conseguido unificar en un mismo documento los criterios de las dos especialidades más implicadas en el manejo de estos pacientes.

Introduction

Laryngopharyngeal reflux (LPR) is a condition of the upper aerodigestive tract caused by the direct or indirect exposure of the pharynx and larynx to gastroduodenal contents, which can trigger morphological and/or neurological alterations in the affected tissues.¹ Although LPR shares some pathophysiological characteristics with gastroesophageal reflux disease (GERD), there are notable differences in its clinical manifestations, diagnostic methods, and response to treatment.^1,2

Its diagnosis remains a challenge, despite its high prevalence in ENT, gastroenterology, and primary care clinics,^3,4 mainly due to the lack of specificity of its symptoms and the absence of objective biomarkers.^5,6

LPR management has been the subject of debate for years. While GERD has had well-defined clinical guidelines and international consensus, LPR has only begun to receive greater attention in recent years.⁷ Limited evidence on the efficacy of proton pump inhibitors (PPIs)⁸ and the lack of universally accepted diagnostic tests have produced discrepancies in its clinical management.⁹

This situation has led to patients with LPR undergoing multiple medical consultations and diagnostic procedures,¹⁰ which not only places a burden on the healthcare system but also negatively impact their quality of life. Furthermore, several studies have demonstrated that chronic laryngeal symptoms are associated with higher levels of anxiety and depression.¹¹

Faced with this uncertainty, a group of specialists in otolaryngology (ENT) and gastroenterology (GI) with experience in the management of LPR and GERD was formed. They met regularly to establish an expert committee and develop a consensus statement on LPR based on scientific evidence and the opinions of physicians from both specialties, using a modified Delphi methodology. The objective of this consensus was to gather criteria for the definition and diagnosis of LPR, and to provide agreed-upon recommendations to help specialists optimise the clinical approach and management of this condition in routine clinical practice.

Materials and methods

The consensus was developed by combining the principles of evidence-based medicine with a modified Delphi approach.¹² The initial items were drafted and proposed by the consensus expert committee (CEC), composed of three otolaryngologists and two gastroenterologists, based on published evidence and their clinical experience. The Delphi process was organised into a maximum of two voting rounds. Physicians from both specialties, selected through a distribution representative of the healthcare practices in the Spanish autonomous communities and with at least five years of experience as specialists, were invited to vote anonymously on the items via an online platform (Survio®, Brno, Czech Republic). Each participant was allowed to complete the survey only once per voting round. Statements not validated in the first round (consensus level <80% but >60%) were improved based on the CEC's feedback for the subsequent round. The establishment of the current consensus was carried out in six steps:

• •

  Meeting of the CEC members and development of the preliminary statement by the CEC.

• •

  Selection of the panel of participating specialists and first round of voting.

• •

  Evaluation of the results by the CEC and preparation of the second set of questions based on the results.

• •

  Presentation of the results of the first and second rounds of voting.

• •

  Evaluation of the results by the CEC and drafting of the final consensus document.

• •

  Drafting of this document and obtaining the endorsement of the Spanish Society of Otolaryngology and Head and Neck Surgery (SEORL-CCC).

Drafting of statements

The CEC experts developed an initial list of 117 items on LPR, covering the following topics: definition, pathophysiology, and differences from GERD (N = 29), main symptoms and pharyngeal findings of LPR (N = 24), associations between LPR and ENT diseases (N = 14), diagnostic methods (N = 18), validated questionnaires (N = 3), common treatments and recommendations (N = 15), and clinical management and follow-up of patients with PLPR (N = 14).

Voting and discussion rounds

The Delphi process began in December 2023 and continued until February 2025. Two rounds of voting were conducted, separated by periods of review and discussion. Items were evaluated using a 5-point scale that included "strongly disagree," "somewhat disagree," "neither agree nor disagree," "somewhat agree," and "strongly agree." Consensus acceptance was defined as agreement (largely agree or strongly agree) by at least 80% of the experts. Statements that received between 60% and 80% agreement were reviewed by the expert committee. Statements that did not reach at least 60% agreement were discarded and were not subject to further review or a related vote.

Participating panellists

A total of 73 panellists from both specialties (60.3% ENT and 39.7% GI) completed the first round of the Delphi study- Of these, 65 (89.0%) completed both rounds (63.1% ENT and 36.9% AD) (Appendix I). The specialists, representative of the Spanish autonomous communities (Fig. 1), had an average of 17 years of experience, and 53.8% practiced in a hospital setting (Table 1).

Figure 1.

Geographical distribution of the participant panellists of the ReFaL project.

Table 1.

Demographic distribution of the participating panellists (N = 65).

Gender [n(%)]
Man	32 (49,2)
Woman	33 (50,8)
Age [years(SD)]	44,3 (9,6)
Speciality [years(SD)]
Otolaryngology	41 (63,1)
Digestive system	24 (36,9)
Experience [years (SD)]	17,0 (9,1)
Place of work [n (%)]
Hospital	35 (53,8)
Hospital + Private	12 (18,5)
Private	7 (10,8)
Hospital + Outpatient + Private	6 (9,2)
Hospital + Outpatient	3 (4,6)
Outpatient + Private	1 (1,5)
Outpatient	1 (1,5)

Results and discussion

After analysing the first round of validation, 48.3% of the items were approved, while in the second round this percentage increased to 74.2% (Fig. 2). The distribution of the percentage of validated items per block in each round is presented in Fig. 3. A salient point of the second round of voting is that 100% of the items in blocks 5, 6, and 7 were accepted. Regarding the classification of the final consensus items, fourteen were related to the definition, pathophysiology, and differences with GERD; twelve were related to the main pharyngeal symptoms and findings of LPR; and two analysed the associations between LPR and various otolaryngological diseases (Table 2). With respect to diagnosis, thirteen items focused on this topic, of which ten analysed the role of different diagnostic methods and three focused on the use of validated questionnaires (Table 2). In the area of ​​treatment and recommendations, fifteen items were dedicated to this aspect. Of these, seven consisted of dietary strategies and lifestyle modifications. The clinical management and follow-up of patients with LPR were addressed in 11 items (Table 2).

Figure 2.

Percentage of items validated and not validated throughout the two voting rounds. In the first round, 48.3% of the items (56) were accepted and 17.2% (20) were rejected. In the second round, 74.2% of the items (66) were validated and 12.4% (11) were rejected.

Figure 3.

Percentage of items validated for each question block across the two voting rounds.

Table 2.

ReFal consensus items.

ITEMS			AGREEMENT
1. Definition, pathophysiology and Differences with Gastroesophageal Reflux Disease (GERD)
1.1 Laryngopharyngeal reflux (LPR) is a condition characterised by symptoms, signs, and morphological changes in the upper aerodigestive tract. These manifestations result from the direct and indirect effects of the retrograde flow of gastroduodenal contents into the pharynx and larynx.			97.0%
1.2 Laryngopharyngeal reflux is also known by several alternative names. The most common is laryngopharyngeal reflux, but it is also known as:
	1.2.1. Extra oesophageal Manifestations of GERD		89.2%
	1.2.2. otolaryngological Manifestations of GERD		78.5%*
1.3. The lack of a clearly agreed-upon definition of LPR makes it difficult to determine its prevalence. Therefore, it is of great interest to define this pathology precisely and reach a consensus, establishing clear criteria or guidelines for its appropriate diagnosis and treatment.			98.5 %
1.4. Gastroesophageal reflux (GER) and LPR share certain common pathophysiological mechanisms. The presence of GER is a risk factor for the development of LPR.			93.9 %
1.5. GER and LPR can manifest with different clinical presentations.			92.5 %
1.6. Up to 60% of patients with LPR do not present with typical GER symptoms, such as:
	1.6.1. Acid regurgitation		86.2 %
	1.6.2. Heartburn		84.6 %
1.7. 1.7. Risk factors that predispose individuals to developing RFL include:
	1.7.1. Early adoption of the supine position after eating		92.3 %
	1.7.2. Alcohol consumption		90.8 %
	1.7.3. Obesity		90.8 %
	1.7.4. Smoking		87.7 %
	1.7.5. Diets high in fats. sugars. and/or acids		89.2 %
	1.7.6. The use of certain medications that contribute to lowering lower oesophageal sphincter pressure		89.2 %
2. Main pharyngeal symptoms and findings of laryngeal reflux disease (LPR)L
2.1. The clinical manifestations of LPR are highly nonspecific, hence the difficulty in its diagnosis and subsequent treatment. Among the most frequent symptoms, with varying degrees of evidence, the following stand out:
		2.1.1. Dry, chronic cough, or cough that appears after lying down or eating	95.4 %
		2.1.2. Throat clearing	90.8 %
		2.1.3. Dysphonia	90.7 %
		2.1.4. Globus sensation	84.6 %
		2.1.5. Laryngeal spasms in the supine position	80.0 %
2.2. The low specificity of the common symptoms in patients with LRD makes accurate diagnosis difficult. Hence the need to establish a differential diagnosis with other infectious, inflammatory, neoplastic, traumatic, and/or neurological pathologies that affect the upper airway and present similar symptoms, such as acute laryngitis, allergies, or asthma, among many others.			100,0 %
2.3. Although the diagnosis of laryngopharyngeal reflux (LPR) should not be based solely on laryngeal findings, it is recommended to perform a laryngeal endoscopic examination in all patients with suspected LPR.			93,8 %
2.4. Oesophageal findings on endoscopy and the results of reflux monitoring studies are very nonspecific. The main pharyngolaryngeal findings associated with LPR include:
		2.4.1. Arytenoid erythema	96.6 %
		2.4.2. Interarytenoid or posterior pachydermia	93.1 %
		2.4.3. Diffuse laryngeal erythema	85.5 %
		2.4.4. Pharyngeal erythema	84.7 %
		2.4.5. Erythema or oedema of the vocal cords	78.0 %*
3. Associations between laryngeal reflux disease (LPR) and otolaryngological diseases
3.1. Numerous associations, with varying degrees of confidence, have been proposed between LRD and different otolaryngological pathologies. However, the limited scientific evidence supporting these potential associations necessitates further studies to establish them with greater certainty.			95.4 %
3.2. In some otolaryngological pathologies, such as laryngeal granuloma, a certain degree of association with LPR has been detected.			83.3 %
4. Diagnostic methods
44.1. Currently, the diagnosis of LPR is clinical and is based on the symptoms reported by patients and pharyngolaryngeal endoscopic findings.			92.3 %
4.2. 24 -h oesophageal pH-impedance monitoring is considered the current gold standard for the diagnosis of LPR.			83.1 %
4.3. Beyond pH-impedance monitoring, diagnostic tests that may aid in the diagnosis of LPR include:
		4.3.1. Empirical treatment or therapeutic trial with PPIs	92,1 %
		4.3.2. Examination of the oral cavity and oropharynx	89,1 %
		4.3.3. Gastrointestinal endoscopy	87,3 %
4.4. Upper gastrointestinal endoscopy alone does not diagnose LPR, as endoscopy often yields no relevant findings in patients with this condition. However, it is useful for ruling out other potential lesions in the patient.			98.5 %
4.5. In patients with suspected LPR, double-channel oesophageal pH monitoring may be useful for diagnosing LPR caused by acid reflux. However, its usefulness is limited for diagnosing the disease caused by non-acid events.			84.6 %
4.6. in healthcare centres where oesophageal pH-impedance measurement is not available, double-channel oesophageal pH-metry helps in the diagnosis of patients with suspected RPR.			76.9 %*
4.7. The severity of perceived LPR on the HEMI-pH does not necessarily correlate with the severity of the patient's symptoms and examination findings.			80.0 %
4.8. The salivary pepsin test (PEP test), currently unavailable in most healthcare facilities, is a rapid, simple, and non-invasive test that detects pepsin in a saliva sample.			88.7 %
5. Validated questionnaires
5.1. The Reflux Symptom Index (RSI) is a nine-item patient-reported outcome questionnaire. This index subjectively assesses the severity and frequency of symptoms on a scale of 0 to 5. A score of 13 or higher indicates that the patient is susceptible to LPR.			98.2 %
5.2. The Reflux Symptom Score (RSS) is a 22-item patient-reported outcome questionnaire. This questionnaire subjectively assesses the potential impact on the patient's quality of life. A shorter version, the RSS-12, appears to be equally effective but quicker to complete. This scale is more consistent than the RSI, although it is less frequently used in otolaryngology clinics. Therefore, it would be beneficial to promote wider use of this questionnaire among specialists, given its greater consistency. 92.7%			92.7 %
5.3. The Reflux Finding Score (RFS) is used to grade the findings obtained with laryngeal endoscopy. This scale evaluates eight items that capture the most common laryngoscopic findings in patients with LPR. The RFS exhibits significant intra- and inter-observer variability, so an image-based guide could help reduce this variability.			98.1 %
6. Common treatments and recommendations
6.1. Lifestyle modifications constitute the first therapeutic intervention in the management of LRF. This approach is considered the best empirical treatment for patients with LPR, regardless of the severity of their symptoms. Furthermore, it stands out for its favourable cost-effectiveness.			90.8 %
6.2. Some patients, especially those without typical GERD symptoms, may be reluctant to follow lifestyle and dietary recommendations because they do not understand that their ear, nose, and throat symptoms are secondary to reflux. In these cases, it may be advisable to also prescribe pharmacological treatment during the initial phases of management (1−2 months).			93.9 %
6.3. Among the most prominent lifestyle and dietary measures for the empirical treatment of patients with LPR are:
		6.3.1. Not eating or drinking for 2 h before vigorous exercise or bedtime.	93,8 %
		6.3.2. Reducing fat intake and avoiding large meals. 93.8%	93,8 %
		6.3.3. Avoid caffeine. alcohol. and nicotine 92.3%	92,3 %
		6.3.4. Raise the bed head	90,8 %
		6.3.5. Try to reduce stress levels	89,2 %
		6.3.6. Lie on your left side when going to bed	87,7 %
		6.3.7. Do not use girdles. belts. or tight clothing around the abdomen	87,7 %
6.4. Proton pump inhibitors (PPIs) are considered very safe for both short- and long-term use. Their potential side effects are well-known and manageable, provided they are prescribed correctly.			96.9 %
6.5. Combining PPIs with alginates could be a viable option to reduce the PPI dose. This combination could help keep disease symptoms under control and shorten the duration of treatment			93.8 %
6.6. In patients with severe LPR, doubling the standard PPI dose may be appropriate. In these cases, administering a single double dose of PPIs on an empty stomach in the morning may be effective; however, from a pharmacokinetic perspective, it seems more advisable to divide the single double dose into two standard doses separated by 12 h, one before breakfast and the other before dinner.			92.3 %
6.7. Alkaline and weak acid reflux are also associated with LPR. Therefore, if empirical treatment with PPIs does not produce a positive response, this should not necessarily exclude the diagnosis of LPR.			87.7 %
6.8. In patients with alkaline and weakly acidic LPR, the use of alginates or the combination of alginates and PPIs may be the most appropriate treatment option.			89.2 %
6.9. Products containing hyaluronic acid and specific barrier agents, such as keratin, have reparative and regenerative properties for damaged epithelium. Furthermore, they play a protective role against oxidative damage and proteolytic enzymes, such as pepsin. These properties make them a promising treatment for repairing and preventing damage caused by LPR.			95.4 %
7. Clinical Management and Follow-up of Patients with LPR
7.1. The management of patients with LPR should be carried out jointly by otolaryngologists and gastroenterologists, given that it is a clinical manifestation of a digestive disease that causes lesions in the ear, nose, and throat			93.8 %
7.2. Although patients with LPR usually present initially in otolaryngology clinics, it is recommended that gastroenterology clinics always investigate, in a targeted manner, the presence of other atypical symptoms and/or extra oesophageal manifestations of GERD. This is the case with LPR, which is the most frequent extra-digestive manifestation of this pathology.			90.8 %
7.3. Given the acute, chronic, or recurrent nature of LPR, patients with this disease will need to maintain prolonged pharmacological treatment (either continuous or intermittent) until symptom control and resolution of the ear, nose, and throat lesions are achieved.			92.3 %
7.4. During follow-up by an otolaryngologist of a patient with LPR, the following should be considered:
		7.4.1. Checking the patient's changes in habits and their stress management	96,8 %
		7.4.2. Adjusting medication if the patient has experienced improvement	95,2 %
		7.4.3. Monitoring the evolution of symptoms by repeating the RSI or RSS questionnaires to check the score before and after treatment	93,4 %
		7.4.4. A physical examination using pharyngolaryngeal endoscopy to observe possible changes in endoscopic signs	86,9 %
7.5. During follow-up by a gastroenterologist of a patient with LPR, the following should be considered:
		7.5.1. Ruling out alarm symptoms (dysphagia. weight loss)	96,6 %
		7.5.2.7.5.3. Monitoring treatment adherence	94,8 %
		7.5.4. Monitoring symptom control	91,4 %
7.6. In patients with treatment-refractory LPR, it is recommended that these cases be jointly assessed by gastroenterologists and otolaryngologists.			96.9 %

*

These items were included by decision of the scientific committee, for various reasons, despite not reaching 80% approval from the panellists.

Definition, Pathophysiology, and Differences with GERD

In our study, with a 97% agreement level, LPR was defined as “a pathology identified by the presence of symptoms, signs, and morphological alterations in the upper aerodigestive tract. These manifestations resulted from the direct and indirect effects of the retrograde flow of gastroduodenal contents into the pharynx and larynx.” This definition incorporates advances in pathophysiological understanding, emphasizing both the direct damaging mechanisms through contact with the mucosa and the indirect effects that can manifest in tissues not directly exposed to the refluxed material.

This definition aligns with other definitions found in the consulted literature. The conceptualisation of LPR has evolved significantly over the years and has been the subject of extensive debate in numerous international scientific forums, notably the definitions established in the IFOS-Dubai Consensus¹³ and the European Consensus for the Management and Treatment of Laryngopharyngeal Reflux Disease.¹ Both agree in describing LPR as a condition affecting the upper aerodigestive tract, caused by direct or indirect exposure to reflux of gastroduodenal contents. This exposure can lead to both structural and functional alterations in the tissues involved. Among the main mediators of mucosal damage are substances such as pepsin, bile acids, elastase, and possibly trypsin, which play a key role in mucosal inflammation and the manifestation of LPR symptoms.^14,15

LPR is also known by several alternative names. The most common is laryngopharyngeal reflux, but it is also referred to as extraesophageal manifestations of GERD and otolaryngological manifestations of GERD.

These terms likely refer to the Lyon consensus for the classification of GERD, where the clinical manifestations of reflux were separated into oesophageal and extraesophageal syndromes.¹⁶

In our study, 98.5% of the panellists agreed that the lack of a clearly agreed-upon definition of LPR makes it difficult to determine its prevalence. Therefore, reaching a consensus that allows for the definition and establishment of clear criteria for its diagnosis and treatment is of great interest.

The lack of a clear definition, coupled with the non-specificity of its clinical manifestations, represents an obstacle to determining its incidence in the population. However, LPR-associated symptoms and events are frequently consulted in primary care, ENT and gastroenterology departments.^7,17,18

Over 90% of the specialist physicians surveyed considered that gastroesophageal reflux (GER) and LPR share certain pathophysiological mechanisms. Furthermore, the presence of GER constitutes a risk factor for the development of LPR, even though both conditions can manifest as different clinical presentations. In fact, up to 60% of patients with LPR do not present typical GER symptoms, such as regurgitation and heartburn.

The pathophysiological mechanisms of GERD have been extensively investigated and are mainly attributed to inappropriate transient relaxation of the lower oesophageal sphincter (LES) or to its hypotonia, which facilitates the retrograde movement of gastric contents into the oesophagus with the consequent appearance of symptoms and/or complications.¹⁹ For its part, LPR is also characterised by a retrograde flow of gastroduodenal contents, but with an extension beyond the upper oesophageal sphincter (UES), reaching the laryngopharyngeal región.²⁰ Consequently, although GERD and LPR share certain pathophysiological mechanisms, they present significant differences in physiological responses and symptomatology. In most cases of LPR, patients do not experience heartburn or regurgitation, symptoms that, in contrast, are characteristic of GERD.²¹ However, the presence of GERD should be considered a contributing factor when assessing the likelihood of LPR. In fact, a possible correlation between the severity of GERD and the development of LPR has been suggested,²² highlighting the importance of a comprehensive evaluation in these patients.

Analysing the results obtained in relation to the main risk factors that predispose to the appearance of LPR, a consensus was reached with an agreement level exceeding 87.5% in all cases. These factors include early adoption of the supine position after eating; alcohol consumption; obesity; and smoking. Diets high in fats, sugars, and/or acids, and the use of certain medications that contribute to decreased lower oesophageal sphincter pressure, are also contributing factors.

Available scientific evidence supports the role of these factors in the pathophysiology of laryngopharyngeal reflux (LPR). Early supine positioning after eating,²³ an inadequate diet, and alcohol consumption have been documented to have a significant impact on gastroesophageal motility and LES pressure.²⁴ Similarly, obesity, smoking, and the use of certain medications also contribute to decreased LES pressure, which promotes reflux of gastroduodenal contents into the laryngopharyngeal region.^25,26

Main Pharyngeal Symptoms and Findings of LPR

There was a consensus that the clinical manifestations of LPR are highly non-specific, hence the difficulty in its diagnosis and subsequent treatment. Among the most frequent symptoms, with varying degrees of evidence, are a dry, chronic cough that worsens when lying down or eating; throat clearing; dysphonia; globus pharyngeus; and laryngeal spasms in the supine position.^21,27

These clinical symptoms derive from an inflammatory process of the mucosa in the upper aerodigestive tract, a common response in various otolaryngological conditions, which complicates diagnosis.^27,28 Hence the need to establish a differential diagnosis with other infectious, inflammatory, neoplastic, traumatic, and/or neurological pathologies that affect the upper airway and present similar symptoms, such as acute laryngitis, allergies, or asthma, among others.

Ninety-three point eight per cent of the panellists agreed that, while the diagnosis of LPR should not be based solely on laryngeal findings, it is advisable to perform a laryngeal endoscopic examination in all patients with suspected LPR. However, like clinical symptoms, endoscopic findings also lack specificity and can occur in various inflammatory diseases affecting the mucosa of the upper aerodigestive tract.²⁹ The main endoscopic findings associated with LPR include arytenoid erythema, interarytenoid or posterior pachydermia, diffuse laryngeal erythema, pharyngeal erythema, and erythema or oedema of the vocal cords.^30–32 These alterations should be interpreted within the clinical context of each patient to optimise the diagnostic process and avoid unnecessary or incorrect treatments.

Associations between LPR and Otolaryngological Diseases

During the development of the consensus, multiple associations, with varying degrees of confidence, have been proposed between laryngeal reflux and different otolaryngological pathologies. However, the limited scientific evidence on these associations underscores the need for future studies to establish them with greater certainty.^31–36

Among the most discussed otolaryngological findings in this context, laryngeal granuloma generated a high degree of consensus (agreement level 83.3%). Several studies have demonstrated that refluxed gastric contents (acid, pepsin, bile) can induce damage to the laryngeal mucosa, particularly in the arytenoid region, triggering chronic inflammatory processes that can manifest as laryngeal granulomas.^37–39

Diagnostic methods

Ninety-two point three per cent of the experts who participated in the study agreed that, currently, the diagnosis of LPR is primarily established through clinical evaluation, based on patient-reported symptoms and pharyngolaryngeal endoscopic findings.¹⁰ However, 24-h oesophageal pH-impedance monitoring (HEMII-pH) remains the current gold standard for diagnostic confirmation of LPR,¹³ although the severity of the pathology determined by HEMII-pH does not always correlate with the severity of symptoms or with the patient's examination findings.^40,41

In centres where HEMII-pH is not available, double-channel oesophageal pH monitoring is considered a useful diagnostic tool for patients with suspected LPR. This recommendation aligns with that included in the European Clinical Practice Guidelines for Otolaryngology, where experts recommended oropharyngeal pH measurement as a complementary tool in cases where HEMII-pH is unavailable.¹ According to these guidelines, the presence of more than 10 episodes of pharyngeal reflux with a pH ≤ 6.0 could be considered indicative of the disease. However, oropharyngeal pH monitoring has not been recognised as the diagnostic standard due to several limitations, including the use of a single sensor and the inability to identify proximal oesophageal events prior to the detection of pharyngeal reflux.^1,40

Since pH measurement using HEMII-pH or oropharyngeal pH is not available in all medical centres, many professionals opt for an empirical approach based on the response to proton pump inhibitor (PPI) treatment.⁴² This approach is usually effective and cost-effective for patients with mild to moderate LPR and no alarm symptoms.¹³

Another alternative method accepted by the panellists was the detection of pepsin in saliva using the salivary pepsin assay (PEP-test), a rapid, simple, and non-invasive technique. However, its availability in healthcare settings is still limited. Although the PEP-test could be considered an auxiliary tool in the diagnosis of LPR, it has certain significant limitations, such as the high variability in the sensitivity of the measurements.^33,43,44 Furthermore, studies have shown inconsistencies in the correlation between salivary pepsin levels, HEMII-pH findings, and clinical manifestations. These discrepancies could be attributed to the possible involvement of other gastroduodenal enzymes in mucosal inflammation and the generation of symptoms.³³

Validated questionnaires

The panellists agreed that patient-reported outcome questionnaires (PROMs) are very useful tools for assessing the severity, frequency, and impact of symptoms on quality of life in various pathologies. Using them optimises both the initial assessment and follow-up after treatment.

In the context of LPR, the Reflux Symptom Index (RSI) is the most widely used instrument. This nine-item self-administered questionnaire allows for the subjective assessment of symptom intensity and frequency on a scale of 0 to 5, with a score of 13 or higher suggesting the possible presence of LPR in the patient.³¹

Another widely used instrument is the Reflux Symptom Score (RSS), composed of 22 items designed to subjectively assess the impact of LPR on the patient's quality of life.⁴⁵ Its abbreviated version, the RSS-12, has proven to be an effective and more agile alternative in terms of completion.⁴⁶ Although the RSS-12 has been noted to be more consistent than the RSI,⁴⁷ its use in otolaryngological clinical practice remains limited. This reflects a discrepancy between recommendations in the literature and the adoption of these instruments in actual clinical practice, suggesting the need for strategies to promote their use.

It is important to emphasize that, while PROMs such as the RSI and RSS allow for the documentation of the presence and evolution of symptoms, they have no diagnostic value in themselves due to the overlap of manifestations with other irritative laryngopharyngeal pathologies. Consequently, these questionnaires have no diagnostic value for laryngopharyngeal reflux disease (LPR), but rather serve to document the presence and evolution of laryngopharyngeal symptoms before and after treatment. Therefore, they cannot replace the available objective diagnostic tools.¹³

Like the symptoms, endoscopic findings in patients with laryngoscopic reflux disease (LRD) have low specificity, as similar inflammatory signs can be observed in multiple diseases of the upper aerodigestive tract. This lack of specificity highlights the need to supplement the evaluation with additional clinical tools.

The Reflux Finding Score (RFS) is one of the most widely used scales for evaluating laryngoscopic findings associated with LPR. This scale enables grading the presence and severity of eight characteristic laryngoscopic signs in patients with suspected LPR.⁴⁸ However, the literature describes significant intra- and interobserver variability in its application, which affects its reproducibility. This discrepancy between the theoretical utility of the RFS and its actual clinical applicability underscores the importance of strategies to improve its reliability, such as implementing the use of image-illustrated guides, a recommendation that was raised by the Clinical Committee during the discussion of the current consensus.

Common treatments and recommendations

Hygienic and dietary modifications represent the first line of therapy in the management of LPR (95.4% agreement among our specialists), and their importance has been widely supported by the literature.^49–51

Adherence to a specific diet for gastroesophageal reflux is important to optimise symptom control and, in the long term, enable the gradual reduction or even discontinuation of pharmacological treatment. Furthermore, implementing lifestyle changes contributes to a decrease in medication dependence.¹

Among the hygienic and dietary measures with the greatest consensus among the panellists for the treatment of LPR are the following: avoiding the intake of food and beverages for at least two hours before intense exercise or at bedtime; reducing fat intake and avoiding large meals, as these can promote reflux; and eliminating or minimising the consumption of caffeine, alcohol, and nicotine, agents that can decrease LES pressure. Elevating the head of the bed can reduce the likelihood of night-time reflux episodes. Stress management is also important, given its potential impact on symptom exacerbation. Sleeping on the left side can help reduce reflux episodes, and patients should avoid wearing girdles, tight belts, or clothing that is constricting around the abdomen, as these can increase intra-abdominal pressure and promote reflux. Weight loss and waiting at least two hours after the last meal or drink are also recommended.^49–51

However, adherence to these modifications varies among patients. A significant proportion do not follow these guidelines, often due to ingrained lifestyle habits or a lack of specific nutritional education. This lack of adherence is particularly common in patients without typical GERD symptoms, as they may not understand that their ear, nose, and throat symptoms are secondary to reflux. In these cases, it was agreed, with nearly 94% consensus, that prescribing pharmacological treatment during the initial phases of management (1−2 months) could be advisable.

Regarding pharmacological treatment, respondents emphasized that PPIs are the cornerstone of LPR therapy.⁵² It was also considered that in patients with severe LPR, doubling the standard PPI dose may be appropriate. In these cases, administering a single double dose of PPI on an empty stomach in the morning may be effective. However, from a pharmacokinetic perspective, it seems more advisable to divide the single double dose into two standard doses separated by 12 h, one before breakfast and the other before dinner.^52,53

Therapeutic de-escalation strategies have been explored, such as combining PPIs with alginates, which could allow for a reduction in the PPI dose without compromising symptom control.⁵⁴ Gastroesophageal reflux disease (GERD), regardless of its weakly acidic or alkaline nature, can be effectively treated with alginates or with alginates in combination with antacids. Alginates form a protective barrier over gastric contents, significantly decreasing episodes of gastroesophageal reflux and reducing the risk of upper aerodigestive tract involvement.^55,56

Additionally, it was agreed with a 95.4% consensus that products containing hyaluronic acid and specific barrier agents, such as keratin, have reparative and regenerative properties for epithelium damaged by GERD. Furthermore, they play a protective role against oxidative damage and proteolytic enzymes, such as pepsin.^57–60

Clinical management and follow-up of patients with LPR

The panellists agreed that the management of patients with GERD requires a multidisciplinary approach, involving close collaboration between specialists in otolaryngology and gastroenterology. Given that pharyngeal reflux (PR) is a manifestation of digestive pathology with repercussions in the otolaryngological field, its diagnosis and treatment should not be limited to a single specialty.¹⁹ This assessment aligns with recent literature highlighting the need for a multidisciplinary approach to managing PR, with close collaboration between otolaryngologists and gastroenterologists.^1,13

While patients often initially consult an otolaryngologist for symptoms such as dysphonia, throat clearing, or a sensation of a foreign body in the pharynx, it is essential that gastroenterologists evaluate the presence of atypical symptoms and extraesophageal manifestations of GERD, with LPR being the most frequent.⁶¹ Identifying and characterising these symptoms allows for optimising the therapeutic approach and improving clinical outcomes.

Given the clinical course of LPR, which can present acutely, chronically, or recurrently, treatment must be individualised and sustained over time. Pharmacological therapy, based primarily on proton pump inhibitors (PPIs) and complementary measures such as dietary modifications and lifestyle changes, should be maintained for an extended period, continuously or intermittently, depending on the patient's progress, until adequate symptom control and resolution of associated lesions are achieved. Although this statement is in line with the literature supporting the use of PPIs in combination with lifestyle modifications and dietary changes,^49–51 there was a lack of consensus among the panellists regarding the optimal duration of PPI treatment, suggesting the need for further studies to establish standardised protocols based on the patient's symptomatic evolution.

It was also agreed that during the follow-up of a patient with LPR, the otolaryngologist should assess lifestyle changes and stress management,⁵⁰ adjust medication if there is improvement,⁶² monitor symptom evolution using the RSI or RSS questionnaires, and perform a laryngopharyngeal endoscopy to detect endoscopic changes.^31,47 Meanwhile, the gastroenterologist should rule out alarm symptoms such as dysphagia or weight loss, verify treatment adherence, and monitor symptom control. In cases refractory to treatment, a joint evaluation between both specialties is recommended.

However, these tools are not used systematically in clinical practice. Furthermore, monitoring treatment adherence and detecting alarm symptoms, such as dysphagia or weight loss, do not appear to be standardised, which could negatively impact the early detection of complications.

Strategies to optimise detection and clinical management

Based on the results obtained in the consensus, several areas for improvement were identified that could optimise the identification, diagnosis, and management of LPR. Although the existence of a clear definition represents significant progress, challenges remain regarding its detection in clinical practice, the uniformity of diagnostic criteria, and the training of healthcare professionals.

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  Once a clear definition is agreed upon, it would be of great interest to conduct prevalence studies that allow for a more precise understanding of the magnitude of LPR in different populations. The collection of reliable epidemiological data would not only facilitate the identification of risk groups but would also contribute to the development of more effective intervention strategies.

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  Given the considerable intra- and inter-observer variability of some current questionnaires, such as the RFS, it would be advisable to develop and validate a simpler and standardised tool. More accessible questionnaires with less subjectivity would facilitate better case identification and greater reproducibility of results, making them easier to use in both clinical settings and research studies.

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  Primary care physicians are the first point of contact for many patients with the healthcare system, so it is important to strengthen their knowledge in this area. Specific training in the detection and management of rhinoplasty would improve early diagnosis and could avoid unnecessary referrals to specialists, thus optimising the resources of the National Health System.

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  Although the RSS-12 has been shown to be more consistent than the RSI-47, its use in otolaryngological clinical practice remains limited. It would be highly advisable to increase the dissemination of this questionnaire among otolaryngologists, as they play a key role in diagnostic confirmation. Ensuring that otolaryngologists are aware of and have access to validated and up-to-date tools could allow for a more accurate and homogeneous diagnosis, reducing variability in the interpretation of results and promoting more appropriate clinical management.

Strengths and limitations of the study

This study has several strengths that reinforce the validity and relevance of its results. First, its multidisciplinary approach stands out, integrating the perspectives of otolaryngologists and gastroenterologists, which is essential given that pleural effusion (PE) lies at the intersection of both specialties. This complementary viewpoint allows for a more comprehensive and precise approach to the pathology.

Furthermore, the broad geographical representation of the panellists, reflecting the healthcare realities of the Spanish autonomous communities, provides a national perspective on the management of PE in Spain. Participants have an average of 17 years of clinical experience, ensuring a high level of knowledge on the subject.

Finally, the rigorous Delphi methodology used lends strength to the results, with clearly defined consensus criteria (80% agreement) and an iterative process that allowed for refining the statements until a high degree of validation was achieved (74.2% in the second round).

However, the study also has certain limitations, such as a slight imbalance in the proportion of participating specialists, with a greater representation of otolaryngologists (63.1%) compared to gastroenterologists (36.9%). This bias in the panel composition could have influenced the orientation of some recommendations toward the otolaryngological perspective.

Conclusion

This study establishes a consensus among otolaryngology and gastroenterology specialists throughout Spain, describing and providing relevant information on the diagnosis, management, and treatment of LPR in Spain, fostering collaborative research and the adoption of common, evidence-based approaches to this disease.

The dissemination of this consensus aims to consolidate expert knowledge in the field, serving as a rigorous and up-to-date reference to improve clinical practice and guide future studies that optimise the management of this pathology.

Funding

Laboratorios CINFA S.A. was the promoter and funder of this project, but did not participate in or influence the opinion of the participants in the preparation of the survey, the statistical analysis, the discussion of the results or in the writing of the article, which were the responsibility of CROSSDATA and the committee of experts who sign as authors of the article on behalf of the ReFaL working group.

Acknowledgements

The authors express their gratitude to CINFA Laboratories S.A. for their unconditional support in carrying out this project, without interfering in the content, development, and drafting of this consensus.

We also thank CROSSDATA, a Contract Research Organization (CRO), whose participation has been essential for the comprehensive development of this work. CROSSDATA has been involved in all phases of the study, providing methodological and technical support, from the conception and design of the project, through the coordination of data collection and analysis, to assistance with the critical interpretation of the results and the preparation of this manuscript.